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Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease (NYMC-571)

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ClinicalTrials.gov Identifier: NCT02675959
Recruitment Status : Recruiting
First Posted : February 5, 2016
Last Update Posted : September 30, 2019
Sponsor:
Collaborators:
University of California, Los Angeles
Medical College of Wisconsin
University of Chicago
Tufts Medical Center
Texas Children's Hospital
Johns Hopkins University
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Brief Summary:
This is a follow-up trial to NYMC 526 (NCT01461837) to assess the safety, efficacy and toxicity of administering Defibrotide prophylaxis for high-risk sickle cell or beta thalassemia patients undergoing a familial haploidentical allogeneic stem cell transplantation with CD34 enrichment and T-cell addback. This patient population historically has a risk of developing sinusoidal obstructive syndrome (SOS) and Defibrotide has demonstrated efficacy in treatment of SOS. The Funding Source is FDA OOPD.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Defibrotide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Prophylactic Defibrotide in Children, Adolescents, and Young Adults With Sickle Cell Disease or Beta Thalassemia Following MAC and Haploidentical Stem Cell Transplantation Utilizing CD34 Enrichment and T-Cell (CD3) Addback
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Defibrotide prophylaxis
defibrotide will be given prior to and during myeloablative immunotherapy conditioning (MAIC) followed by familial haploidentical (FHI) allogeneic stem cell transplantation (AlloSCT) with CD34 enrichment and t-cell addback in patients with high-risk sickle cell disease or beta thalassemia to reduced the risk and rate of the development of sinusoidal obstructive syndrome (SOS).
Drug: Defibrotide
defibrotide will be given prophylactically prior to AlloSCT to determine if it decreases the incidence of SOS in this high risk population, and determine that it is safe and feasible to give along with myeloimmunoablative therapy and allogeneic transplant.




Primary Outcome Measures :
  1. All patients will be monitored for known and unknown side effects of defibrotide with daily physical exams while in the hospital and then as needed in addition to daily laboratory values including chemistries, hematology labs as needed [ Time Frame: 100 days ]
    Patients will be given Defibrotide prophylaxis starting 10 days before the stem cell infusion at 6.25 mg/kg IV q6h and continue through Day +21.

  2. All patients will be monitored for the development of SOS. [ Time Frame: 1 year ]
    All patients will get daily lab values while in patients and then as needed to monitor for elevation in liver function tests and other abnormal chemistry or hematology values. Imaging on the liver will be performed as needed to determine if they develop SOS with defibrotide.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 34 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must demonstrate one or more of the following Sickle Cell Disease Complications (or patients in Cohort 2 can meet other high risk criteria instead)
  • Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
  • Acute chest syndrome in the preceding two year period prior to enrollment that have failed, been non-compliant or declined hydroxyurea treatment, or prior to chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis.
  • Recurrent painful events (at least 3 in the 2 years prior to enrollment or prior to chronic chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis).
  • Abnormal TCD study requiring starting on chronic transfusion therapy and/or exchange transfusions.
  • At least one silent infarct lesion on a MRI scan of the head. Or (directly or probably related to SCD)
  • Sickle Cell nephropathy;
  • Splenic sequestration requiring RBC transfusion;
  • Aplastic crisis requiring RBC transfusion;
  • Avascular necrosis of the hip diagnosed by MRI;
  • Two episodes or more of leg ulcerations;
  • Recurrent priapism .
  • Infant dactylitis.

    • OR for Cohort #2 ONLY: Patient must be between 18 and 34.99 years of age, patients must demonstrate at least two of the following:
  • WBC > 13,500 cells/microliter at baseline when not acutely ill (on two separate occasions) > 2 weeks from a VOC event or hospitalization.
  • Tricuspid Regurgitant Jet Velocity (TRV) > 3.0 m/s
  • Requiring Chronic Monthly Transfusions ( > 12 transfusions in the 12 months)
  • History of sepsis
  • N-terminal pro-brain natriuretic peptide (NT-proBNP) > 160 ng/L at clinical baseline when not acutely ill or hospitalized.
  • all patients must meet disease, age, organ function and donor criteria;

Exclusion Criteria:

  • Females who are pregnant or breast-feeding are not eligible
  • SCD Patients with documented uncontrolled infection at the time of study entry are not eligible.
  • SCD patients who have an unaffected HLA matched family donor willing to proceed to donation will not be eligible for this study.
  • Karnofsky or Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
  • Demonstrated lack of compliance with medical care.
  • Patients with clinically significant fibrosis or cirrhosis of the liver will not be eligible.
  • Patients who have previously received a HSCT will not be eligible.
  • Patients with contraindications to the use of defibrotide

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02675959


Contacts
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Contact: Mitchell S Cairo, MD 914-594-2150 Mitchell_Cairo@nymc.edu
Contact: Erin Morris, RN 714-964-5359 erin_morris@nymc.edu

Locations
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United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Theodore B Moore, MD    310-825-6708    tbmoore@mednet.ucla.edu   
Contact: Andres Vargas    310-794-8929    AndresVargas@mednet.ucla.edu   
Principal Investigator: Theodore B Moore, MD         
United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109-1274
Contact: Ghada Abusin, MD         
Principal Investigator: Ghada Abusin, MD         
United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Sandra Fabricatore, RN, PNP    914-594-2152    sandra.fabricatore@wmchealth.org   
Contact: Erin Morris, RN    714-964-5359    erin_morris@nymc.edu   
Principal Investigator: Mitchell S Cairo, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Julie A Talano, MD    414-955-4185    jtalano@mcw.edu   
Principal Investigator: Julie A Talano, MD         
Sponsors and Collaborators
New York Medical College
University of California, Los Angeles
Medical College of Wisconsin
University of Chicago
Tufts Medical Center
Texas Children's Hospital
Johns Hopkins University
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Mitchell Cairo, MD New York Medical College

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Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT02675959     History of Changes
Other Study ID Numbers: NYMC 571
4090 ( Other Grant/Funding Number: OPD )
First Posted: February 5, 2016    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mitchell Cairo, New York Medical College:
stem cell transplantation
sickle cell disease
haploidentical
defibrotide
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Defibrotide
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors